The overall objective is to establish whether there is a functional microangiopathy which occurs in the retina of diabetic patients in response to tissue hypoxia. The recognition of compensatory changes in the retinal circulation would support a recent concept of the pathogenesis of diabetic retinopathy which has led to treatment based on the manipulation of the oxyhaemoglobin dissociation curve using dietary phosphate. The biochemical changes that are present in uncontrolled juvenile diabetics with ketoacidosis and the alterations which follow treatment with insulin provide a suitable opportunity to investigate the autoregulatory capacity of the retinal circulation in a reversible situation of tissue hypoxia. The retinal circulation will be studied by the photographic estimation of relative blood fluorescence concentration and the construction of dye dilution curves from which the mean retinal cirulation time can be derived by conventional formulae. Tissue hypoxia will be assessed by measurements of the P50 in vivo of the oxyhaemoglobin dissociation curve and the factors which influence it such as plasma phosphate, 2, 3-DPG, haemoglobin concentration, haematocrit, PO2, pH and percent HbO2.